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Contains fulltext : 219533.pdf (Publisher’s version ) (Closed access) Medical students' attitudes towards patients with addiction and towards other chronic conditions might be comparable. Positive attitudes towards such conditions can be developed during medical education. This study evaluated medical students' attitudes towards patients with addiction, dementia, and diabetes, and how such attitudes change during training. This is an observational prospective cohort study. Participants (N = 100) were students who recruited from Primary and Community Care training, which consisted of theoretical courses and a clinical rotation. The Medical Condition Regard Scale was used to measure the attitudes and a repeated-measures analysis was performed to compare them. Before training, students' attitudes towards patients with addiction were more negative than towards dementia and diabetes. The attitudes towards addiction remained stable during the entire training, whereas the attitudes towards dementia and diabetes remained stable during the theoretical courses but decreased after the clinical rotation. These findings emphasize a need to pay attention to students’ attitude development towards patients with chronic diseases, addiction in particular, during medical training. 11 p.

Contains fulltext : 248940.pdf (Publisher’s version ) (Open Access) BACKGROUND: Understanding the genetic underpinnings of antidepressant treatment response in unipolar major depressive disorder (MDD) can be useful in identifying patients at risk for poor treatment response or treatment resistant depression. A polygenic risk score (PRS) is a useful tool to explore genetic liability of a complex trait such as antidepressant treatment response. Here, we review studies that use PRSs to examine genetic overlap between any trait and antidepressant treatment response in unipolar MDD. METHODS: A systematic search of literature was conducted in PubMed, Embase, and PsycINFO. Our search included studies examining associations between PRSs of psychiatric as well as non-psychiatric traits and antidepressant treatment response in patients with unipolar MDD. A quality assessment of the included studies was performed. RESULTS: In total, eleven articles were included which contained PRSs for 30 traits. Studies varied in sample size and endpoints used for antidepressant treatment response. Overall, PRSs for attention-deficit hyperactivity disorder, the personality trait openness, coronary artery disease, obesity, and stroke have been associated with antidepressant treatment response in patients with unipolar MDD. LIMITATIONS: The endpoints used by included studies differed significantly, therefore it was not possible to perform a meta-analysis. CONCLUSIONS: Associations between a PRS and antidepressant treatment response have been reported for a number of traits in patients with unipolar MDD. PRSs could be informative to predict antidepressant treatment response in this population, given advances in the field. Most importantly, there is a need for larger study cohorts and the use of standardized outcome measures.

Contains fulltext : 237816.pdf (Publisher’s version ) (Open Access) BACKGROUND: Low-grade inflammation occurs in a subgroup of patients with Major Depressive Disorder (MDD) and may be associated with response to antidepressant medications. The Neutrophil to Lymphocyte Ratio (NLR) and total White Blood cell Count (WBC) are markers of systemic inflammation which have not been investigated as predictors for outcome to pharmacotherapy in unipolar depression yet. Moreover, the association between inflammation and treatment response has not been studied in unipolar Psychotic Depression (PD). We conducted an exploratory analysis to examine the prognostic significance of NLR and WBC in pharmacotherapy of PD. METHODS: Baseline NLR and WBC were examined in their association with response to seven weeks of treatment with antidepressants (venlafaxine or imipramine) and the combination of an antidepressant with an antipsychotic (venlafaxine plus quetiapine) in 87 patients with PD. Logistic regression models were adjusted for age, gender, Body Mass Index (BMI), depression severity, duration of the current episode and number of previous depressive episodes. Secondary outcomes were remission of depression and disappearance of psychotic symptoms. RESULTS: Higher NLR was associated with increased response to pharmacotherapy (Exp(B) 1.66, 95 % CI 1.03-2.66, p = 0.036), but not with remission of depression or disappearance of psychotic symptoms. WBC was not associated with any of the outcome measures. CONCLUSION: NLR may be a novel, inexpensive and widely available biomarker associated with response to pharmacotherapy in PD. The association between white blood cell measures and treatment outcome should be further investigated for different types of antidepressants in PD and in non-psychotic MDD.

Contains fulltext : 205536.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Catatonia is a syndrome that can present in different forms and can occur in multiple psychiatric and somatic conditions. This case report describes lethal catatonia caused by delayed toxic leukoencephalopathy after excessive use of cocaine and methadone. The characteristic radiographic imaging and biphasic course are discussed. CASE REPORT: A 54-year-old woman was presented unconsciously at the emergency department after intoxication with methadone and cocaine. After initial recovery, her condition deteriorated unexpectedly, resulting in lethal catatonia. Magnetic resonance imaging (MRI) showed hyperintense white matter abnormalities and diffusion restriction, evident for leukoencephalopathy. DISCUSSION: Catatonia can develop in multiple psychiatric and somatic diseases, including toxic leukoencephalopathy. A biphasic course and specific MRI findings are characteristics for delayed toxic leukoencephalopathy, due to intoxication with drugs. 4 p.

Background Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. Methods A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. Results Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. Conclusions Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased.

Contains fulltext : 229924.pdf (Publisher’s version ) (Open Access) BACKGROUND: Psychomotor Retardation is a key symptom of Major Depressive Disorder. According to the literature its presence may affect the prognosis of treatment. Aim of the present study is to investigate the prognostic role of Psychomotor Retardation in patients with unipolar Psychotic Depression who are under antidepressant treatment. METHODS: The Salpetriere Retardation Rating Scale was administered at baseline and after 6 weeks to 122 patients with unipolar Psychotic Depression who were randomly allocated to treatment with imipramine, venlafaxine or venlafaxine plus quetiapine. We studied the effects of Psychomotor Retardation on both depression and psychosis related outcome measures. RESULTS: 73% of the patients had Psychomotor Retardation at baseline against 35% after six weeks of treatment. The presence of Psychomotor Retardation predicted lower depression remission rates in addition to a higher persistence of delusions. After six weeks of treatment, venlafaxine was associated with higher levels of Psychomotor Retardation compared to imipramine and venlafaxine plus quetiapine. CONCLUSIONS: Our data confirm that Psychomotor Retardation is a severity marker of unipolar Psychotic Depression. It is highly prevalent and predicts lower effectivity of antidepressant psychopharmacological treatment.

Contains fulltext : 173890.pdf (Publisher’s version ) (Closed access) Detailed neurobehavioural profiles are of major value for specific clinical management, but have remained underexposed in the population with intellectual disabilities (ID). This was traditionally classified based on IQ level only. Rapid advances in genetics enable etiology based stratification in the majority of patients, which reduces clinical heterogeneity. This paper illustrates that specific profiles can be obtained for rare syndromes with ID. Our main aim was to study (mal)adaptive functioning in Kleefstra Syndrome (KS) by comparing and contrasting our findings to three other subgroups: Koolen-de Vries Syndrome, GATAD2B-related syndrome, and a mixed control group of individuals with ID. In total, we studied 58 individuals (28 males, 30 females) with ID; 24 were diagnosed with KS, 13 with Koolen-de Vries Syndrome, 6 with the GATAD2B-related syndrome, and 15 individuals with undefined neurodevelopmental disorders. All individuals were examined with a Vineland Adaptive Behavior Scale, mini PAS-ADD interview, and an Autism Diagnostic Observation Schedule to obtain measures of adaptive and maladaptive functioning. Each of the three distinctive genetic disorders showed its own specific profile of adaptive and maladaptive functioning, while being contrasted mutually. However, when data of the subgroups altogether are contrasted to the data of KS, such differences could not be demonstrated. Based on our findings, specific management recommendations were discussed for each of the three syndromes. It is strongly suggested to consider the genetic origin in individuals with congenital neurodevelopmental disorders for individual based psychiatric and behavioral management. 10 p.

Unsupervised learning is often used to obtain insight into the underlying structure of medical data, but it is not always clear how to use such structure in an effective way. In this paper, we propose a probabilistic framework for predicting disease dynamics guided by latent states. The framework is based on hidden Markov models and aims to facilitate the selection of hypotheses that might yield insight into the dynamics. We demonstrate this by using clinical trial data for psychotic depression treatment as a case study. The discovered latent structure and proposed outcome are then validated using standard depression criteria, and are shown to provide new insight into the heterogeneity of psychotic depression in terms of predictive symptoms for different interventions.

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion. © 2015, The Author(s). Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Display Omitted New model for non-homogeneous time process that extends dynamic Bayesian networks.Incremental learning heuristic avoids overfitting, including the scarce data case.The approach is neither sampling-based nor assumes smooth transitions.Extensive simulations learnt fitter (non-)homogeneous models than state of the art.Better fitted models and new clinical insights drawn on psychotic depression case. For many clinical problems in patients the underlying pathophysiological process changes in the course of time as a result of medical interventions. In model building for such problems, the typical scarcity of data in a clinical setting has been often compensated by utilizing time homogeneous models, such as dynamic Bayesian networks. As a consequence, the specificities of the underlying process are lost in the obtained models. In the current work, we propose the new concept of partitioned dynamic Bayesian networks to capture distribution regime changes, i.e. time non-homogeneity, benefiting from an intuitive and compact representation with the solid theoretical foundation of Bayesian network models. In order to balance specificity and simplicity in real-world scenarios, we propose a heuristic algorithm to search and learn these non-homogeneous models taking into account a preference for less complex models. An extensive set of experiments were ran, in which simulating experiments show that the heuristic algorithm was capable of constructing well-suited solutions, in terms of goodness of fit and statistical distance to the original distributions, in consonance with the underlying processes that generated data, whether it was homogeneous or non-homogeneous. Finally, a study case on psychotic depression was conducted using non-homogeneous models learned by the heuristic, leading to insightful answers for clinically relevant questions concerning the dynamics of this mental disorder.

Background: Genetic mosaicism is only detected occasionally when there are no obvious health or developmental issues. Most cases concern healthy parents in whom mosaicism is identified upon targeted testing of a genetic defect that was initially detected in their children. A germline genetic defect affecting the euchromatin histone methyltransferase 1 (EHMT1) gene causes Kleefstra syndrome, which is associated with the typical triad of distinct facial appearance, (childhood) hypotonia, and intellectual disability. A high degree of psychopathology is associated with this syndrome. A few parents with a mosaic EHMT1 mutation have been detected upon testing after a child was diagnosed with a germline EHMT1 defect. At first glance, carriers of a mosaic EHMT1 mutation appeared to function normally. However, recent studies have shown that de novo, postzygotic mutations in important developmental genes significantly contribute to autism spectrum disorder (ASD). Therefore, we hypothesized that EHMT1 mosaicism could cause neuropsychiatric defects. To investigate this, we performed a detailed investigation of cognitive neuropsychiatric parameters in parents identified with EHMT1 mosaicism.Methods: Three adults (two males, one female) with a genetically confirmed diagnosis of EHMT1 mosaicism were examined by means of a battery of tests and observational instruments covering both neurocognitive and psychiatric features. The battery included the following instruments: the Autism Diagnostic Observation Schedule (ADOS), the mini Psychiatric Assessment Schedules for Adults with Developmental Disabilities (mini PAS-ADD), the Vineland Adaptive Behavior Scales (VABS), and the Cambridge Neuropsychological Test Automated Battery (CANTAB). These measures were compared with our previously reported data from Kleefstra syndrome patients with confirmed (germline) EHMT1 defects.Results: All three subjects achieved maximum total scores on the VABS, indicative of adequate (adaptive) functioning. In all, scores above cutoff were found on the ADOS for ASD and on the mini PAS-ADD for major depressive disorder (lifetime). Finally, results on the CANTAB showed impaired cognitive flexibility in all subjects.Conclusion: Individuals with EHMT1 mosaicism seem to have increased vulnerability for developing severe psychopathology, especially ASD and mood disorders. Although at first glance they appear to be well-adapted in their daily functioning, they may experience significant psychiatric symptoms and show reduced cognitive flexibility in comparison to the general population.

Objective: Electroconvulsive therapy (ECT) is still the most effective treatment of severe and therapy-refractory major depressive disorder. Cognitive side effects are the major disadvantage of ECT. Cognitive deficits are generally temporary in nature and may be mediated by the hippocampus. Recent studies have shown a temporary increase in hippocampal volume and a temporary decrease in cognitive functioning post-ECT compared with pre-ECT. This study investigates whether these volumetric changes are related to changes in cognitive functioning after ECT.Methods: Nineteen medication-free patients with treatment-resistant major depressive disorder underwent a whole-brain magnetic resonance imaging scan and a neuropsychological examination (including the Rey auditory verbal learning task, Wechsler Memory Scale Visual Reproduction, fluency, Trail Making Task) within 1 week before and within 1 week after the course of ECT. Electroconvulsive therapy was administered twice a week bitemporally with a brief pulse. A matched healthy control group (n = 18) received the same neuropsychological examination and at a similar interval to that of the patients.Results: Hippocampal volumes increased significantly from pretreatment to posttreatment in patients. Mean performance on cognitive tasks declined, or remained stable, whereas performance in controls generally improved because of retesting effects. The increase in hippocampal volume was related to changes in cognitive performance, indicating that this increase co-occurred with a decrease in cognitive functioning.Conclusions: Our findings tentatively suggest that the temporal increase in hippocampal volume after treatment, which may result from neurotrophic processes and is thought to be crucial for the antidepressive effect, is also related to the temporary cognitive side effects of ECT.

Contains fulltext : 153372.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

Contains fulltext : 208448.pdf (Publisher’s version ) (Closed access) The pharmacokinetics of many antidepressants (tricyclic antidepressants (TCA) or selective serotonin re-uptake inhibitors (SSRI)) are influenced by the highly polymorphic CYP2D6 enzyme. Therefore, pharmacogenetics could play an important role in the treatment of depressive patients. The potential cost-utility of screening patients is however still unknown. Therefore, a Markov model was developed to compare the strategy of screening for CYP2D6 and subsequently adjust antidepressant treatment according to a patient's metabolizer profile of poor, extensive, or ultra metabolizer, with the strategy of no screening ('one size fits all' principle). Each week a patient had a probability of side effects, which was followed by dosage titration or treatment switching. After 6 weeks treatment effect was evaluated followed by treatment adjustments if necessary, with a total time horizon of the model of 12 weeks. The analysis was performed from a societal perspective. The strategy of screening compared with no screening resulted in incremental costs of euro91 (95 percentiles: euro39; euro152) more expensive but also more effect with 0.001 quality adjusted life years (QALYs) (95 percentiles: 0.001; 0.002) gain. The incremental cost-effectiveness ratio (ICER) was therefore euro77,406 per QALY gained, but varied between euro22,500 and euro377,500 depending on the price of screening and productivity losses. According to our model, we cannot unequivocally conclude that screening for CYP2D6 in primary care patients using antidepressants is be cost-effective, as the results are surrounded by large uncertainty. Therefore, information from ongoing studies should be used to reduce these uncertainties.

Contains fulltext : 175699.pdf (Publisher’s version ) (Closed access) Intellectual disability is frequently accompanied by psychiatric symptoms that require pharmacological interventions. Treatment guidelines often provide a general treatment approach for these symptoms in intellectual disability. However, this may not always be the best strategy, as illustrated here in Kleefstra syndrome. We present 3 patients showing severe regression after sleep disturbances. If these are treated with care as usual (eg, behavioral programs and sleep medication) deterioration is likely to follow. It is observed that rapid treatment with relatively high dosages of antipsychotics contributes to restore sleep, halt further regression, and improve daily life functioning. 4 p.

Contains fulltext : 177350.pdf (Publisher’s version ) (Closed access) The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 x 10-8; rs191260602, P=3.9 x 10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case-control sample with the categorical phenotype PD/AG (Ncombined =1012) obtaining highly significant P-values also for GLRB single-nucleotide variants rs17035816 (P=3.8 x 10-4) and rs7688285 (P=7.6 x 10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

van de Ven AC, Muntjewerff J-W, Netea-Maier RT, de Vegt F, Ross HA, Sweep FCGJ, Kiemeney LA, Vos PE, Buitelaar JK, Hermus ARMM, den Heijer M, Janzing JGE. Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression. Objective: The aim of this study was to investigate whether thyroid function and thyroid peroxidase antibodies (TPOAb) are associated with depression, when using both state and trait parameters of depression. Method: In 1125 participants of the Nijmegen Biomedical Study, thyroid-stimulating hormone (TSH), free thyroxine (FT(4) ), and TPOAb were measured twice. The Beck Depression Inventory (BDI), a self-reported lifetime diagnosis of depression, and the neuroticism scale of the Eysenck Personality Questionnaire Revised Short Scale (EPQ-RSS) were used to evaluate the presence of state and trait features of depression. Results: We found no association between TSH and FT(4) levels and BDI score, current depression, lifetime diagnosis of depression, and EPQ-RSS neuroticism score. Subjects with TPOAb had higher EPQ-RSS neuroticism scores in comparison with subjects without TPOAb, mean score 4.1 vs. 3.2 (regression coefficient 0.70; 95% CI 0.1-1.3; P-value 0.02 after adjustment for confounders). The prevalence of a lifetime diagnosis of depression was higher in subjects with positive TPOAb in comparison with participants without TPOAb: 24.2% vs. 16.7% (relative risk 1.4; 95% CI 1.0-2.1; P-value 0.04 after adjustment for confounders). Conclusion: Thyroid peroxidase antibodies are positively associated with trait markers of depression. The presence of TPOAb may be a vulnerability marker for depression.

Item does not contain fulltext Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP ( approximately 2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 x 10(-8) ) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 x 10(-6) ) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. (c) 2012 Wiley Periodicals, Inc. 01 september 2012

Contains fulltext : 173921.pdf (Publisher’s version ) (Closed access) Last December, Dr. Havdahl et al. highlighted the use of autism spectrum disorder (ASD) symptom measurements in specific groups in their article "Multidimensional Influences on Autism Symptom Measures: Implications for Use in Etiological Research". This is an important and timely topic, because public attention is currently tuned to the increasing prevalence of ASD. Dr. Havdahl et al. carefully mapped which of the tested instruments was most sensitive to detect actual ASD symptoms and to distinguish these from other typical comorbid neurodevelopmental disorders, such as intellectual disability (ID) and attention-deficit/hyperactivity disorder. 2 p.

Contains fulltext : 88967.pdf (Publisher’s version ) (Closed access) BACKGROUND: Research examining the course of depressive symptoms during electroconvulsive therapy (ECT) is relatively scarce. OBJECTIVE: To classify patients according to the course of their depressive symptoms while receiving ECT. METHODS: The sample consisted of 156 consecutive patients receiving ECT for unipolar depressive disorder. Depressive symptoms were measured weekly with the Montgomery-Asberg Depression Rating Scale. Latent class analysis was applied to identify distinct trajectories of symptom improvement. RESULTS: We identified five classes of different trajectories (improvement rates) of depressive symptoms, i.e. fast improvement (39 patients), intermediate improvement (47 patients), slow improvement (30 patients), slow improvement with delayed onset (18 patients), and finally a trajectory with no improvement (20 patients). The course of depressive symptoms at the end of the treatment within the trajectories of intermediate improvement, slow improvement and slow improvement with delayed onset, was still improving and did not achieve a plateau. CONCLUSION: The different courses of depressive symptoms during ECT probably contribute to mixed results of prediction studies of ECT outcome. Data suggest that for a large group of patients no optimal clinical endpoint can be identified, other than full remission or no improvement at all, to discontinue ECT. 01 juli 2010

Contains fulltext : 87624.pdf (Publisher’s version ) (Closed access) OBJECTIVE: It remains unclear whether unipolar psychotic depression should be treated with an antidepressant and an antipsychotic or with an antidepressant alone. METHOD: In a multi-center RCT, 122 patients (18-65 years) with DSM-IV-TR psychotic major depression and HAM-D-17 > or = 18 were randomized to 7 weeks imipramine (plasma-levels 200-300 microg/l), venlafaxine (375 mg/day) or venlafaxine-quetiapine (375 mg/day, 600 mg/day). Primary outcome was response on HAM-D-17. Secondary outcomes were response on CGI and remission (HAM-D-17). RESULTS: Venlafaxine-quetiapine was more effective than venlafaxine with no significant differences between venlafaxine-quetiapine and imipramine, or between imipramine and venlafaxine. Secondary outcomes followed the same pattern. CONCLUSION: That unipolar psychotic depression should be treated with a combination of an antidepressant and an antipsychotic and not with an antidepressant alone, can be considered evidence based with regard to venlafaxine-quetiapine vs. venlafaxine monotherapy. Whether this is also the case for imipramine monotherapy is likely, but cannot be concluded from the data. 01 maart 2010

Apathy and depression are common neuropsychiatric features of Huntington's disease. The authors studied a group of 34 Huntington's disease patients. In addition to the conventional classification according to DSM-IV criteria of depression, emphasis was put on a dimensional approach using scores on several different scales. Severe depression was found in 12% and severe apathy in 52% of all study patients. The authors found that apathy and depression are not related and are clearly distinct dimensions. Apathy was related to disease characteristics such as cognitive deterioration and functional decline, whereas depression was not.

Contains fulltext : 76985.pdf (Publisher’s version ) (Closed access) Objectives: The serotonin transporter gene (5-HTT) has been proposed as a candidate gene for major depressive disorder (MDD). Association studies, however, have revealed inconsistent results. This could be because of the phenotypic heterogeneity of MDD, as it often presents with comorbid disorders such as generalized anxiety disorder (GAD), alcohol-related disorders, and dysthymia. Methods: In this exploratory study, we performed regression analyses with generalized estimating equations in patients with familial MDD (n=233) in order to explore whether a polymorphism in the serotonin transporter gene (5-HTTLPR) is differentially associated with MDD and a comorbid disorder compared with MDD without that particular comorbidity. As in general, GAD is more common in females and alcohol-related disorders are more common in males, the analyses were stratified for sex. Results: Comorbid dysthymia was less common in s-allele carriers with MDD (P

Major depressive disorder (MDD) aggregates in families and is associated with high rates of lifetime axis-I comorbidity. This study examined whether familiality of MDD is associated with the presence of specific comorbid disorders, which might be an important factor to be taken into account in MDD treatment and research into MDD etiology. A population sample was divided into subjects with familial (f-MDD; n = 432) and nonfamilial MDD (nf-MDD; n = 454). Since, more comorbidity was expected in clinical cases, a clinical sample with f-MDD (n = 120) was also studied. Subjects were assessed with the Composite International Diagnostic Interview and family history methods. Binary logistic regression analyses were carried out to examine the influence of familiality of MDD on comorbidity. Analyses were adjusted for potential confounders, including MDD characteristics such as severity and age of onset. Dysthymia, anxiety disorders, and alcohol use disorders were significantly more prevalent in subjects with f-MDD than in subjects with nf-MDD. Clinical f-MDD was associated with more anxiety disorders and fewer alcohol use disorders than population f-MDD. After adjustment for MDD characteristics including age at onset, severity, and disease course, comorbid disorders remained more prevalent in f-MDD than in nf-MDD. The instruments used in the population and the clinical samples were not identical, however, they were comparable to a substantial degree. F-MDD, especially in clinical cases, appears to increase the risk of development of comorbid disorders, regardless of MDD characteristics. The link between familiality and comorbidity is important because it will aid a better understanding of the MDD phenotype, and it contributes to planning of effective treatment and to molecular genetic studies.

BackgroundA number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales.MethodThe 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery–Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores.ResultsThe MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely ‘observed mood and anxiety’, ‘cognitive’ and ‘neurovegetative’, provided a more detailed description of depression severity.ConclusionsThe MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.

Contains fulltext : 52551.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Testing the hypothesis that depressive symptoms in dementia reflect dysfunction in fronto-subcortical pathways. BACKGROUND: Both depression and dementia can be the result of vascular damage of the brain. The nature of the depressive symptomatology seems to be related to concommittant cognitive disturbances in that subjects show more so-called motivational symptoms of depression. These symptoms can be the result of frontal-subcortical dysfunction. It could be very helpful for clinical practice if these subjects could be identified by simple diagnostic procedures. METHODS: Associations were computed between measures of depressive symptoms and a set of neuropsychological tests in a sample of 54 subjects with a post-stroke dementia. RESULTS: Although we used an extensive set of neuropsychological tests, most subjects were able to participate only in a small part of them, because of disease severity. Our hypothesis was supported by a negative correlation between scores on the verbal semantic fluency task and the total numbers of motivational depressive symptoms. None of the neuropsychological tests was significantly related to the number of mood symptoms neither did they correlate with the total number of depressive symptoms. CONCLUSION: This study gives further evidence for the assumption that motivational-based depressive symptoms partially originate from fronto-subcortical dysfunction.

Item does not contain fulltext Depression may be a prognostic marker of subsequent cognitive decline in patients with dementia. Earlier investigations did not find support for this hypothesis but have mainly considered syndromal depression. In this prospective study thirty-two subjects with mild dementia were followed up for 12 months. The effects of GMS-AGECAT syndromal depression, subsyndromal depression and dimensions of depressive symptoms on cognitive functioning after 12 months were studied. A baseline diagnosis of syndromal or subsyndromal depression did not affect cognitive functioning at follow up, but the numbers of mood symptoms predicted slower cognitive decline. Possibly, the report of depressive symptoms by subjects with mild dementia reflects relative intactness of cognitive functions, not accounted for by cognitive screening instruments.

Contains fulltext : 48208.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is unknown to what extent depression and cognitive dysfunction are related in subjects with dementia. A limitation of earlier studies is that only general measures of depression have been studied. METHODS: In a sample of 60 subjects with dementia according to DSM-III-R criteria depressive symptoms were divided into factors of mood and motivation disturbance according to a principal components analysis. Correlations were computed between the factor scores and the performance on a number of specific neuropsychological tests. As the symptom content of motivation disturbance suggests subcorticofrontal dysfunction it was hypothesized that this factor is related to impaired executive functions. RESULTS: 77% of the depressive symptoms contributed to the dimension of motivation disturbance and most of these symptoms occurred outside the context of a major depressive episode. Our hypothesis was supported by a significant negative correlation between motivation symptoms and semantic verbal fluency. This relationship seems to have specificity, as both the dimensions of mood symptoms and of general depressive symptoms did not correlate significantly with specific neuropsychological test scores. CONCLUSIONS: The division of depressive symptoms in factors of mood and motivation disturbance contributes to insight into the relationship between depression and cognitive dysfunction in dementia. An advantage of the motivation disturbance factor compared to the regular apathy scales is that it consists of depressive symptoms. Therefore, it becomes evident that apathy or impaired motivation may occur in patients with dementia both in and outside the context of a depressive syndrome.

The phenomenology of behavioural disturbances in Huntington's disease remains a topic of discussion. A new, dimensional approach could promote better understanding of these disturbances, as was advocated in a recent paper on the future of neuropsychiatry. The challenge will be to integrate information from different fields and to avoid reductionistic categorisations. Synthesis of this information re-emphasises the diagnosis of ‘organic personality change’ in Huntington's disease. Purpose of review This article reviews the literature of the past two years with regard to the phenomenology of behavioural and psychiatric disturbances in Huntington's disease. Recent findings A dimensional approach to behavioural disturbances in Huntington's disease sheds new and useful light on this subject. Symptom clustering reveals an ‘apathy’ cluster, which is closely related to other parameters of the illness, and two other clusters (an ‘irritability’ cluster and a ‘depression’ cluster) that are not. Other frequently encountered phenomena include aggressiveness, irritability, and obsessive or compulsive symptoms. A relationship between different symptom clusters and neuropsychological test results was found, again most significantly with the apathy cluster.

Item does not contain fulltext OBJECTIVE: To study the presence of different dimensions of depression in subjects with vascular dementia. BACKGROUND: After a stroke, cognitive, affective and behavioural disturbances are common. It has been suggested that the nature of affective symptomatology can help to differentiate organic from psychological depression. METHODS: Cognitive and affective symptoms were assessed in 78 stroke patients and a principal component analysis was performed on these symptoms. Also, a discriminant analysis was carried out to establish the contribution of different symptoms on the diagnosis 'depressive disorder' and 'dementia'. RESULTS: (1) Principal component analysis revealed three distinct sub-syndromes: one with predominantly mood symptoms, one with essentially psychomotor symptoms, and one with vegetative symptoms; (2) mood, psychomotor and vegetative symptoms were all independently and strongly related to a diagnosis of major depressive disorder according to DSM-III-R criteria; (3) the psychomotor factor was also firmly associated with dementia; and (4) discriminant analysis gave further support for our conclusion that some of the depressive features, in particular the psychomotor factor, are at least partly related to the organic brain damage from stroke. CONCLUSION: The results indicate that different dimensions of depression could be discerned in a group of stroke patients and that the symptom profile of depression in these patients can be affected by the presence of dementia.

Objective To compare depression in subjects with and without dementia, adjusting for possible confounders. Background The results of comparisons of depression between subjects with and without dementia are inconclusive. Probably confounders play a role. Methods Ninety-one subjects with DSM-III-R dementia and 110 controls without dementia were recruited from homes for the elderly using an identical procedure. The prevalences of AGECAT depressive syndromes, subsyndromes and factors of depressive symptoms were compared adjusting for possible confounders. Results (1) Both groups had similar prevalences of AGECAT depressive syndromes, subsyndromes and overall rates of depressive symptoms; (2) subjects with dementia had significantly more ‘motivation symptoms’; and (3) there was a trend to a lower prevalence of ‘mood symptoms’ in subjects with dementia. These results refer to a sample of institutionalised elderly subjects. It is not clear to what extent they can be generalised to subjects living in the community. Conclusion The results indicate that it is not AGECAT (sub)syndrome measures of depression but the profile of depressive symptomatology which is affected by dementia. Copyright © 2002 John Wiley & Sons, Ltd.

Objective: This study was designed to compare the efficacy of three two-phase pharmacological treatment strategies for inpatients with DSM-IV-TR major depressive disorder with psychotic features. Method: During phase I, 122 patients participated in a 7 week double-blind eight center study comparing imipramine (dose adjusted to target plasma levels of 200300 ng/ml), venlafaxine (maximum 375 mg/day) and venlafaxine-quetiapine (maximum 375 mg/day; 600 mg/day). Four centers participated in phase II. In phase II, for patients without treatment response or with partial response, lithium was added to phase I pharmacotherapy. Lithium dose was adjusted to a target serum level of 0.6-1.0 mmol/l. Final evaluation of remission and response was made after 4 weeks of lithium addition. Results: Since only 15 patients were included in phase II, evaluation of the twophase treatment strategies was impossible, and lithium addition was evaluated as an open study. Lithium addition appeared remarkably effective, since 9 of 15 (60%) attained remission, defined as a final Hamilton Depression Rating Scale (HAM-D) score≤ 7. The same number of patients achieved response (HAM-D reduction ≥ 50%). All 9 remitters had a sustained remission during a four-month follow-up period. Conclusion: Lithium addition appears to be remarkably effective in psychotic depression, but these data from an open study are insufficient evidence for this treatment to be considered evidence based. Trial registration: http://www.controlled-trials.com/isrctn/trial ISRCTN36607067 An open study of lithium addition in refractory psychotic depression 109

Background. Little is known about the effects of depression on the mortality rates of elderly subjects with dementia.Methods. Logistic regression analysis, adjusting for possible confounders, was used to study the associations between GMS-AGECAT derived syndrome and symptom measures and 12-month mortality rates in a cohort of 73 elderly subjects who met the DSM-III-R criteria of dementia with a median MMSE score of 19.Results. Twenty-three subjects (32%) died within the 12 month follow-up period. A baseline diagnosis of syndromal or subsyndromal depression was associated with increased mortality. At the symptom level mortality was predicted by higher scores on the factor ‘mood symptoms’. The effects of interactions between depression measures and severity of dementia were not significant.Conclusions. Short-term mortality in elderly subjects with less severe dementia is predicted by the presence of (sub) syndromal depression and by mood symptoms. The effects of depression and severity of dementia on the mortality rates seem to be largely independent.

In order to investigate the relationship between cognitive function and daily used drugs in the elderly we performed an observational, cross–sectional study in 5 homes for the elderly in the region of Nijmegen, the Netherlands. Participants were 497 residents of these homes. For all these subjects the daily used drugs, classified according to the Anatomical Therapeutic Classification system, were registered and global cognitive function was measured as the total score on the Mini Mental State Examination. Adjusting for age and education, there was a small but significant and positive correlation between the use of metoprolol and the total MMSE score. The use of CNS drugs was not related to the total MMSE score. All eleven most frequently used drugs together explained 2.9% of the variance in the MMSE scores. These results indicate that there is a negligible association between daily drug use and cognitive function in these subjects.

Contains fulltext : 136881.pdf (Publisher’s version ) (Closed access) Brain-Derived Neurotrophic Factor (BDNF) serum levels are abnormally low in depressed patients as compared to healthy controls and normalize with SSRI treatment. The aim of this study is to examine serum BDNF levels in late-life depression, stratified for SSRI usage, and to explore the relation between BDNF levels and specific depression characteristics as well as between BDNF levels and early and recent life stressors in late-life depression. We assessed serum BDNF levels in 259 depressed patients not using an SSRI, 99 depressed patients using an SSRI and 119 non-depressed controls (age range 60-93 years). Depressive disorders were diagnosed with the Composite International Diagnostic Interview (CIDI, version 2.1). Serum BDNF levels were significantly higher in depressed patients who used an SSRI compared to depressed patients not using SSRIs and compared to non-depressed controls, when adjusted for age, sex, life style characteristics, cognitive functioning and somatic comorbidity. Recent life-events, assessed with the List of Threatening Events-Questionnaire, were significantly associated with lower BDNF levels in non-depressed subjects only. Although a summary score of early traumatization (before the age of 16 years) was not associated with serum BDNF levels in any of the three groups, we found an interaction between a history of severe physical abuse and SSRI usage in the depressed group. Interestingly, higher serum levels of BDNF in depressed patients using SSRIs were only found in those patients without a history of severe childhood abuse and not in those with a history of severe childhood abuse.

Contains fulltext : 168330.pdf (Publisher’s version ) (Open Access) Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.

Contains fulltext : 115410.pdf (Publisher’s version ) (Open Access) According to cognitive theories of depression, individuals susceptible to depression attend selectively to negative information. The purpose of the study was to examine if such an affective processing bias is present in never-depressed individuals with a family history of major depressive disorder (MDD). Formerly depressed female patients having at least one first-degree relative with a history of MDD (n=23), their never-depressed female siblings (n=21) and never-depressed female controls (n=21) performed a conventional and an emotional Stroop task using negative, positive and neutral words. A significant effect was found of group on negative processing bias; post hoc comparisons indicated that never-depressed siblings showed a larger negative processing bias than never-depressed controls. No significant differences were observed in positive bias or conventional interference between the three groups. Our findings suggest that never-depressed females with a family history of depression, like depressed patients, have more difficulties to inhibit negative material and to direct their attention towards task-specific material. This adds to the existing evidence that affective processing bias is a trait characteristic that contributes to the onset of depression and that could be a useful endophenotype for MDD. 5 p.

Item does not contain fulltext BACKGROUND: Depression has been frequently reported in individuals with Down Syndrome (DS). The aim of this article is to provide a comprehensive, critical review of the clinically relevant literature concerning depression in DS, with a focus on epidemiology, potential risk factors, diagnosis, course characteristics and treatment. METHODS: We searched the PUBMED database (January 2011) using the keywords ("Depressive Disorder [MESH]" OR "Depression [MESH]" OR "depress* [All Fields]") AND ("Down Syndrome [MESH]" OR "Down syndrome [All Fields]" OR "Down's syndrome [All Fields]"). Review articles not adding new information, single case reports and papers focusing on subjects other than depression in DS were excluded. RESULTS: The PUBMED search resulted in 390 articles, of which 30 articles were finally included. Recent information does not support earlier suggestions of an increased prevalence of depression in DS compared to other causes of Intellectual Disability (ID). However, individuals with DS show many vulnerabilities and are exposed to high levels of stressors that could confer an increased risk for the development of depression. Apart from general risk factors, several potential risk factors are more specific for DS, including smaller hippocampal volumes, certain changes in neurotransmitter systems, deficits in language and working memory, attachment behaviours and frequently occurring somatic disorders. Protective factors might play a role in reducing the vulnerability to depression. The diagnosis of depression in DS is mainly based upon observable characteristics, and therefore, the use of modified diagnostic criteria is advised. Although several common treatments, including antidepressants, electroconvulsive therapy and psychotherapy seem effective, there is evidence of undertreatment of depression in DS. CONCLUSIONS: There are important limitations to our current clinical knowledge of depression in DS. Future studies should include systematic evaluations of pharmacotherapeutic and psychotherapeutic interventions.

Item does not contain fulltext OBJECTIVE: Vascular disease and neuroticism are both risk factors for late-life depression. In this study we examined the interaction between vascular disease and neuroticism as determinants of clinically relevant depressive symptoms (CRDS) in late-life. METHODS: Multivariate logistic regression in a survey of 1396 population-dwelling people aged >/=70 years. CRDS were defined as scoring >/=16 on the CES-D. Vascular disease was categorised into four levels: none, >/=2 vascular risk factors, cardiac disease or stroke. RESULTS: Neuroticism was strongly associated with CRDS in women (OR: 1.6, 95% CI: 1.4-1.8). In men vascular disease interacted negatively but significantly with neuroticism (cardiac disease by neuroticism: OR: 0.8, 95% CI: 0.6-0.9; stroke by neuroticism: OR: 0.8, 95% CI: 0.6-0.96) when predicting CRDS. CONCLUSIONS: In men vascular disease attenuates the predictive value of neuroticism in CRDS, which might be mediated by apathy caused by cerebrovascular disease.

Contains fulltext : 87295.pdf (Publisher’s version ) (Closed access) BACKGROUND: Data about follow-up after acute pharmacological treatment of psychotic depression are scarce. METHODS: A 4 month open follow-up was done, preferentially with same medication as during acute treatment, of patients (n=59) with DSM-IV-TR major depressive disorder with psychotic features, aged 18 to 65 years, who had completed as responders an acute double-blind 7 week trial with imipramine, venlafaxine or venlafaxine plus quetiapine. Main outcome measures were Hamilton Rating Scale for Depression and Clinical Global Impression Scale. RESULTS: Six patients dropped out during the 4 month follow-up. Almost all patients (86.4%; 51/59) remained responder while remission rate increased from 59.3% (35/59) to 86.8% (46/53), independent of treatment. Relapse rate was low (3.8%; 2/53). Tolerability was good. Weight increased with all treatments. LIMITATIONS: Limitations were the limited sample size and consequent limited statistical power. The treatment during follow-up was not double-blind. CONCLUSIONS: Continuation treatment with the same medication that was effective in the acute treatment trial, remained effective during the 4 month follow-up in many patients leading to further improvement, and was well tolerated. 01 juni 2010

Contains fulltext : 87689.pdf (Publisher’s version ) (Closed access) Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR(MET), 95% CI; 1.27 (1.10-1.47); OR(MET/MET), 95% CI; 1.67 (1.19-2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest. 01 maart 2010

Contains fulltext : 80725.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Although associations between family history and depression have been shown in clinical patients, it is unknown if they also apply to subjects living in the community. The present study considers the relationship between family loading and depression phenotype characteristics in a large community-based sample. METHOD: In a Dutch representative population sample of 7,076 individuals, lifetime diagnosis of depression was classified according to severity, course and age of onset. A family loading score of depression (FLSD) was computed by taking the proportion of the first-degree relatives for whom a history of depression was reported. RESULTS: There was a strong association between FLSD and lifetime diagnosis of MDD. Severity, recurrence and early onset of depression were the specific phenotypic characteristics associated with familiality. The effects of FLSD and gender were independent. CONCLUSION: Associations between family history and risk for depression in the community confirm those reported from clinical-based studies using direct interviewing of relatives. A stronger degree of familiality is associated with specific phenotypic characteristics of depression. 8 p.

Item does not contain fulltext OBJECTIVE: Gender differences exist in the prevalence and psychiatric comorbidity of major depressive disorder (MDD). This study investigates whether familiality of MDD contributes to observed gender differences in comorbidity. METHOD: Familial (f-MDD) and non-familial (nf-MDD) MDD cases from a population sample were assessed for comorbid dysthymia, anxiety disorders and alcohol-related disorders using the Composite International Diagnostic Interview (CIDI). Logistic regression analyses were performed to examine the effect of f-MDD on gender differences in comorbidity, adjusted for confounders. RESULTS: Women with f-MDD reported significantly more comorbid dysthymia and generalized anxiety disorder (GAD) than their male counterparts; women with nf-MDD reported significantly more comorbid simple phobias and agoraphobia than their male counterparts. Gender differences in comorbid panic disorder and alcohol-related disorders occurred independently of the familial load. Adjustment for age of onset, severity and recurrence of MDD did not change these results. CONCLUSION: Models to explain comorbidity patterns of MDD differ by gender. Familiality of MDD should be taken into account. 9 p.